Abstract B34: A randomized open-label phase 2 trial of gemcitabine with or without bavituximab in patients with previously untreated stage IV pancreatic cancer.

Abstract

Background: Despite recent advances in the treatment of metastatic pancreatic cancer, there remains a critical need to develop novel therapeutic strategies that are more effective and less toxic than standard chemotherapy. Targeting the tumor microenvironment in pancreatic cancer may impair tumor growth and metastases. Bavituximab is a monoclonal antibody directed against phosphatidylserine (PS), an anionic membrane phospholipid. PS is absent from normal endothelial cell surfaces. However, in the tumor microenvironment, vascular endothelial cells externalize PS on the cell surface in response to stress conditions resulting from hypoxia and reactive oxygen species. Bavituximab selectively binds to PS on pre-existing tumor blood vessels and limits tumor blood flow. Preclinical data in orthotopic pancreatic tumors in mice indicate that gemcitabine (G) increases PS exposure and the addition of bavituximab may augment the anti-tumor effect by targeting the tumor9s vascular support. Based on promising preclinical and phase I data of the combination of G plus bavituximab it is expected this combination will produce enhanced antitumor activity compared to G alone in patients with advanced pancreatic cancer. Methods: The current randomized open-label, controlled, multicenter phase 2 study is evaluating the addition of bavituximab to standard first line G compared with G alone in patients with Stage IV pancreatic carcinoma. Patients are randomized at a ratio of 1:1 and stratified by CA 19-9 level Citation Format: Shuchi Sumant Pandya, Lucas Wong, Tony R. Reid, Stephen A. Grabelsky, Merrill Kingman Shum, Kerstin B. Menander, Joseph Shan. A randomized open-label phase 2 trial of gemcitabine with or without bavituximab in patients with previously untreated stage IV pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B34.